ORGANOFLUORINE COMPOUNDS OF BIOLOGICAL INTEREST VIA SELECTIVE FLUORINATIONS

该项目将探索合成途径，以产生 通过选择性氟化的生物活性C-氟化化合物。 将氟结合到有机体系中通常具有 对底物的生物活性有显著影响。主要 重点将放在使用二氟化氙作为选择性的 氟化试剂，尽管其他亲电试剂也可能 使用。要研究的主要化合物类别包括碳水化合物、N- 杂环、核苷和脂类。 具体目标包括大量产生新材料 足以进行生物测试和/或开发更好的路线 已知活性的化合物。这些路线可以与F-18一起使用 反应物产生有价值的化合物，涉及放射性同位素 正电子发射断层扫描等应用。为了促进这些 定向合成，将努力更好地理解 选择性氟化作用的机理，特别是了解 催化剂对工艺区域选择性的影响。此外 对于简单的圆周率键的氟化，其他物种的共同加成 将对醇、胺、水和硫醇进行调查，导致 氟烷氧基化等，通过以下途径得到芳香族氟化物 由于芳香族化合物的氟化作用，将对有机金属进行研究 环通常极大地增强生物活性，并直接通过途径完成 这是有限的。 所使用的方法是合成有机和机械有机的标准方法 化学反应。各种色谱技术(气相色谱、高效液相色谱和薄层色谱) 将用于化合物的分析、分离和分离。 结构表征将通过以下几个步骤完成 光谱技术(核磁共振、MS、FT-LR、UV)。细菌的生物学检测 生成的化合物将通过与 药物化学领域的专家。

This project will explore synthetic routes to the generation of biologically active C-fluorinated compounds via selective fluorinations. The incorporation of fluorine into an organic system often has a pronounced effect on the biological activity of the substrate. Primary focus will be on the use of xenon difluoride as the selective fluorination reagent, although other electrophilic reagents may also be used. Key classes of compounds to be studied include carbohydrates, N- heterocycles, nucleosides, and lipids. Specific aims include the generation of new materials in quantities sufficient for biological testing and/or the development of better routes to compounds of known activity. These routes could be used with F-18 reactants to generate compounds of value involving radioisotopes for applications such as positron emission tomography. To facilitate these directed syntheses, efforts will be made to better understand the mechanism of the selective fluorinations and in particular to learn the effects of catalysts on the regioselectivity of the process. In addition to simple fluorination of pi bonds, the co-addition of other species such as alcohols, amines, water and thiols will be investigated leading to fluoroalkoxylation, etc. Routes to aromatic fluorinations via organometallics will be investigated since fluorination of the aromatic ring often greatly enhances bioactivity and direct routes to accomplish this are limited. The methods used are those standard to synthetic and mechanistic organic chemistry. A variety of chromatographic techniques (GC, HPLC, and TLC) will be used for the analysis, separation and isolation of compounds. Structural characterization will be accomplished through several spectroscopic techniques (NMR, MS, FT-lR, UV). The biological testing of the resulting compounds will be carried out by arrangement with specialists in the area of medicinal chemistry.